Understanding Development Safety Update Reports (DSURs): A Dermalexiin Case Study
By Femi Fajimi | 16 July 2025
Introduction: The Role of DSURs in Clinical Drug Development
In clinical development, the safety of trial participants is of paramount importance. To ensure that investigational products are being evaluated responsibly, regulatory authorities require annual safety updates that provide a comprehensive overview of a drug’s evolving risk profile. The Development Safety Update Report (DSUR) serves this purpose.
Mandated under the ICH E2F guideline, DSURs harmonise global expectations around the annual reporting of safety data for investigational medicinal products. They replace or align with older national formats, such as the IND Annual Report in the United States and the Annual Safety Report (ASR) in the EU.
This report is critical to demonstrating that a sponsor is continually assessing the safety of the investigational product in light of accumulating data. For medical writers involved in clinical development, understanding how to structure and craft a DSUR is essential.
To illustrate this, I’ll use a fictional investigational product, Dermalexiin, a topical anti-inflammatory cream under development for moderate-to-severe atopic dermatitis. This example demonstrates how each section of the DSUR is populated and interpreted, aligning with real-world expectations.
DSUR Structure and Guidance Basis
The content and structure of the DSUR are guided by ICH E2F: “Development Safety Update Report” and detailed in regional requirements, such as the EU CT-3 guidance and the FDA IND regulations (21 CFR 312.33).
A standard DSUR consists of:
- Introduction
- Worldwide Marketing Authorisation Status
- Actions Taken for Safety Reasons
- Changes to Investigator’s Brochure
- Line Listing of Serious Adverse Reactions (SARs)
- Cumulative Summary Tabulations
- Summary of Significant Findings from Clinical and Nonclinical Studies
- Safety Signal Evaluation
- Benefit-Risk Evaluation
- Conclusions and Actions
- Appendices
Let’s explore these sections through the lens of Dermalexiin’s first-year DSUR submission (fictional, for educational purposes).
1. Introduction
This section sets the context. It includes information on the DSUR reporting period, sponsor name, product name, active substance, therapeutic area, and the scope of reporting.
Example:
- DSUR Period: 01 July 2024 – 30 June 2025
- Sponsor: Zuurrelin Biosciences Ltd.
- Product Name: Dermalexiin (DMLX-1)
- Indication: Moderate-to-severe atopic dermatitis
- Development Phase: Phase II
- Countries: UK, Germany, Netherlands (EU CT number: 2024-002567-12)
- Clinical Trials Covered: DMLX-AD-201 (Phase IIa), DMLX-AD-202 (ongoing Phase IIb)
2. Worldwide Marketing Authorisation Status
Although Dermalexiin is not yet approved in any country, this section confirms its investigational status and provides a summary of all clinical trial applications and approvals.
Example:
“As of 30 June 2025, Dermalexiin has not been granted marketing authorisation in any territory. It remains under investigation in two EU Member States under the EU CTR (536/2014). No applications have been filed outside the EU.”
3. Actions Taken for Safety Reasons
This section summarises regulatory, sponsor-initiated, or investigator-led actions due to safety concerns.
Example:
“During the reporting period, no clinical holds, protocol modifications, or product withdrawals were implemented for Dermalexiin. A temporary pause in enrolment for Site 104 (Germany) was initiated in February 2025 following an unrelated SAE (pneumonia) but was lifted after safety reassessment.”
4. Changes to the Investigator’s Brochure (IB)
This section documents whether the IB was updated based on new nonclinical or clinical safety data.
Example:
“The IB for Dermalexiin was updated in April 2025 (Version 3.0) to include results from a 13-week dermal toxicity study in minipigs. The observed reversible epidermal thickening was included in Section 7.2. No changes were made to the risk profile.”
5. Line Listings of Serious Adverse Reactions (SARs)
This section includes a line listing of all serious adverse reactions (SARs) reported during the DSUR period. While the actual line listing is appended, a summary is provided in the body.
Example:
“During the reporting period, 8 SARs were reported in 6 subjects. All occurred in subjects receiving the 1% strength formulation. The most frequently reported SAR was localised skin infection (3 cases). No deaths or life-threatening events were observed.”
6. Cumulative Summary Tabulations
Summary tables present an aggregated view of all serious adverse events (SAEs) and adverse reactions observed.
Table: Cumulative Summary of SAEs – Dermalexiin (since first dosing)
| System Organ Class | Preferred Term | Related | Number of Cases |
| Skin and subcutaneous | Dermatitis flare | Yes | 4 |
| Infections | Cellulitis | Yes | 2 |
| General disorders | Application site pain | Yes | 1 |
| Infections | Upper respiratory tract infection | No | 3 |
7. Summary of Significant Findings from Clinical and Nonclinical Studies
Here, new findings from animal or human studies are summarised, particularly those relevant to safety.
Example:
“In a recently completed 90-day repeat-dose dermal toxicity study in minipigs, transient erythema and increased transepidermal water loss were observed at high-dose sites. These effects were reversible post-treatment. No systemic toxicity was detected.”
“In Phase IIa (DMLX-AD-201), transient burning sensation was reported in 12% of subjects receiving active treatment, compared to 3% on placebo. This event was generally mild and resolved within 30 minutes.”
8. Safety Signal Evaluation
This section evaluates new or ongoing safety signals, including the rationale for considering them as signals and any planned investigations.
Ongoing Signal: Application Site Infection
- Description: Three cases of cellulitis were reported within 7 days of drug application
- Assessment: All occurred at the 1% dose. No systemic exposure or fever was observed.
- Action: Enhanced local infection monitoring was added to the protocol for Phase IIb.
9. Benefit-Risk Evaluation
This is a qualitative assessment that balances current knowledge of risks versus benefits, based on available efficacy and safety data.
Example:
“The benefit-risk profile of Dermalexiin remains favourable. Although a potential signal of localised infection is being monitored, no serious systemic safety concerns have emerged. Efficacy results from DMLX-AD-201 show clinically meaningful reductions in EASI scores compared to placebo.”
10. Conclusions and Actions
The concluding section summarises overall findings and outlines any actions planned for the next reporting period.
Example:
“Dermalexiin continues to demonstrate an acceptable safety profile. No dose adjustments are warranted. Safety monitoring will continue, with an added focus on skin infection assessment, in the upcoming Phase IIb trial. The next DSUR will cover the period 01 July 2025 – 30 June 2026.”
11. Appendices
These typically include:
- Line listings of SARs
- Cumulative summary tables
- Protocol numbers and trial status
- IB amendment history
- Literature references
Final Thoughts
Writing a DSUR is a central responsibility for regulatory medical writers involved in ongoing clinical development. It requires cross-functional input from pharmacovigilance, clinical operations, safety physicians, and regulatory leads, as well as a firm grasp of clinical data interpretation.
Through this Dermalexiin case study, I’ve illustrated how structured and detailed a real-world DSUR might look. Understanding the expectations behind each section of the DSUR empowers medical writers to contribute meaningfully to patient safety and product development compliance.
Key References
- ICH E2F Guideline: Development Safety Update Report
- European Commission, Volume 10 of EudraLex
- FDA 21 CFR 312.33 – IND Annual Reports
'Femi Fajimi 
Leave a comment